Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM9QU5Y)

• Drug Name: GSK343 Drug Info
• Synonyms: compound 6 [PMID 24900432]; GSK 343

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 71268957
  ChEBI ID: CHEMBL2204995
  CAS Number: CAS 1346704-33-3
  TTD Drug ID: DM9QU5Y

Molecule-Related Drug Atlas

Drug(s) Targeting Enhancer of zeste homolog 1 (EZH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DS-3201b	DMI69E5	T-cell leukaemia	2A90	Phase 2	[3]
DS-3201	DMRLPFG	Acute lymphoblastic leukaemia	2A85	Phase 1	[4]
HH2853	DMQIE58	Non-hodgkin lymphoma	2B33.5	Phase 1	[5]

Drug(s) Targeting Enhancer of zeste homolog 2 (EZH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tazemetostat	DMWP1BH	Follicular lymphoma	2A80	Approved	[6]
DS-3201b	DMI69E5	T-cell leukaemia	2A90	Phase 2	[3]
CPI-1205	DM3XWJ8	Prostate cancer	2C82.0	Phase 1/2	[4]
SHR2554	DMMUCH0	Prostate cancer	2C82.0	Phase 1/2	[7]
CPI-0209	DMJEXLI	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[8]
DS-3201	DMRLPFG	Acute lymphoblastic leukaemia	2A85	Phase 1	[4]
HH2853	DMQIE58	Non-hodgkin lymphoma	2B33.5	Phase 1	[5]
GSK2816126	DMJDVW4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
PF-06821497	DML3WT6	Diffuse large B-cell lymphoma	2A81	Phase 1	[10]
PMID28394193-Compound-56	DMQRFZK	N. A.	N. A.	Patented	[11]

Drug(s) Affected By Endoribonuclease Dicer (DICER1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[12]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[13]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[14]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[15]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[16]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Amphotericin B	DMTAJQE	Acne vulgaris	ED80	Approved	[19]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[20]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Enhancer of zeste homolog 1 (EZH1)	TTNJA0C	EZH1_HUMAN	Inhibitor	[1]
Enhancer of zeste homolog 2 (EZH2)	TT9MZCQ	EZH2_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Endoribonuclease Dicer (DICER1)	OTTVSEY0	DICER_HUMAN	Gene/Protein Processing	[2]

References

• [1] Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6.
• [2] Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER. Nat Commun. 2014 Oct 29;5:5203. doi: 10.1038/ncomms6203.
• [3] Development of new agents for peripheral T-cell lymphoma. Expert Opin Biol Ther. 2019 Mar;19(3):197-209.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [7] Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov. 2021 Apr;20(4):265-286.
• [8] ClinicalTrials.gov (NCT04104776) A Study of CPI-0209 in Patients With Advanced Tumors. U.S. National Institutes of Health.
• [9] National Cancer Institute Drug Dictionary (drug id 756211).
• [10] Optimization of Orally Bioavailable Enhancer of Zeste Homolog 2 (EZH2) Inhibitors Using Ligand and Property-Based Design Strategies: Identification of Development Candidate (R)-5,8-Dichloro-7-(methoxy(oxetan-3-yl)methyl)-2-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (PF-06821497). J Med Chem. 2018 Feb 8;61(3):650-665.
• [11] EZH2 inhibitors: a patent review (2014-2016).Expert Opin Ther Pat. 2017 Jul;27(7):797-813.
• [12] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [15] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [16] miR-148a/LDLR mediates hypercholesterolemia induced by prenatal dexamethasone exposure in male offspring rats. Toxicol Appl Pharmacol. 2020 May 15;395:114979. doi: 10.1016/j.taap.2020.114979. Epub 2020 Mar 29.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [19] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [20] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [21] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.